Native Aortic Root Thrombosis in Hypoplastic Left Heart Syndrome: An Unusual Presentation (Soon after Atrial Septal Stenting) of a Relatively Unusual Complication—Experience and Literature Review with an Outlook to Diagnosis and Management

We started with the experience of thrombus formation in the native aorta of a 3-year-old male child with hypoplastic left heart syndrome (HLHS) and severely hypoplastic but patent mitral and aortic valves after Glenn palliation, which occurred soon after left heart decompression by percutaneous stenting of the atrial septum. The diagnosis was incidental, with the child completely asymptomatic, and progressively subsided in a few days with heparin infusion and chronic warfarin therapy. We reviewed the incidence, diagnosis, and management of native aortic thrombosis in HLHS after different stages of Fontan palliation through a systematic literature search. In all 32 cases, native aortic thrombosis in HLHS was found. The HLHS anatomic subtypes included mitral stenosis/aortic stenosis (fourteen cases or 45.2%), mitral stenosis/aortic atresia (eleven cases or 35.5%), and mitral atresia/aortic atresia (four cases or 12.9%). The age at diagnosis ranged from 13 days to 18 years. Clinical presentation varied from incidental findings, chest pain and/or electrocardiographic abnormalities, cardiac arrest, and transient ischemic attack. Diagnosis was feasible in most of the cases with only transthoracic echocardiography. Mostly (59.4%), patients were treated with anticoagulation, while others underwent surgical (18.7%), direct (12.5%), or systemic (9.3%) thrombolysis. Transplant-free survival was 56.2%, and fatal events occurred in 25%. Major events occurred in 26.3% of those treated with anticoagulation, in 33.3% of patients treated with surgical/systemic thrombolysis, and in 100% of patients treated with direct thrombolysis. In summary, native aortic thrombosis in HLHS may occur at different ages, with a wide spectrum of presentation from incidental finding to a sudden major event. Diagnosis is feasible with transthoracic echocardiography, and management with anticoagulation is effective despite the incidence of major events remaining high.

We herein describe an unusual case of sudden formation of a thrombus in the native aorta of a child with HLHS after an interatrial stenting procedure.We also provide a literature review on the incidence, diagnosis, and management of native aortic thrombosis in HLHS after different stages of Fontan palliation.

Experience
Data acquisition and analysis were performed in compliance with protocols approved by the Ethical Committee of the Meyer Hospital (ethical approval number 62/2016).Written informed consent was obtained from all participants prior to this study.
A 3-year-old, 15 kg child with HLHS (with severely hypoplastic but patent mitral and aortic valves) and restrictive foramen ovale after the first stage of Nowood-Sano palliation and subsequent Glenn anastomosis at 6 months of age, was admitted for elective percutaneous interatrial stenting.He had previously undergone percutaneous angioplasty for the patent foramen ovale (PFO) at the age of 18 months, as a bridge to the stenting procedure.
The procedure was performed under general anesthesia and echocardiographic guidance.The restrictive PFO was successfully dilated to 10 mm with an Andrastent (26 mm) (Andramed GmbH Schiesswieslenst, Reutlingen, Germany) decreasing the atrial gradient from 8 to 3 mmHg.The baby was weaned from mechanical ventilation in the intensive care unit (ICU) and put under unfractionated heparin (100 UI/kg) and acetylsalicylic acid (5 mg/kg) [3,4].Then, he was sent to the ward in good clinical conditions and with a mild increase in oxygen saturation (from 80 to 85%).Echocardiography performed the day after the procedure revealed a significant improvement of the transatrial flow.However, despite the lack of clinical findings and a normal electrocardiogram (ECG) (Supplementary Figure S1), the pre-discharge echocardiography, performed three days after the procedure, imaged a large thrombus within the native aortic root (Figures 1 and 2, Videos S1 and S2).Thus, the baby was monitored in ICU and put under low weight heparin (LWE) infusion (25 UI/Kg/h) in view of chronic anticoagulation therapy (warfarin 0.2 mg/Kg) [3,4].Partial resolution of the clot was documented after 72 h, and it was completed after 6 days of therapy (Figure 3, Videos S3 and S4).LWE was stopped after 96 h, and the baby was discharged under warfarin therapy after a few days without clinical and instrumental findings.Of interest, no high-sensitivity (hs) troponin-T rise was noted in serial blood test examinations.
We herein describe an unusual case of sudden formation of a thrombus in the native aorta of a child with HLHS after an interatrial stenting procedure.We also provide a literature review on the incidence, diagnosis, and management of native aortic thrombosis in HLHS after different stages of Fontan palliation.

Experience
Data acquisition and analysis were performed in compliance with protocols approved by the Ethical Committee of the Meyer Hospital (ethical approval number 62/2016).Written informed consent was obtained from all participants prior to this study.
A 3-year-old, 15 kg child with HLHS (with severely hypoplastic but patent mitral and aortic valves) and restrictive foramen ovale after the first stage of Nowood-Sano palliation and subsequent Glenn anastomosis at 6 months of age, was admitted for elective percutaneous interatrial stenting.He had previously undergone percutaneous angioplasty for the patent foramen ovale (PFO) at the age of 18 months, as a bridge to the stenting procedure.
The procedure was performed under general anesthesia and echocardiographic guidance.The restrictive PFO was successfully dilated to 10 mm with an Andrastent (26 mm) (Andramed GmbH Schiesswieslenst, Reutlingen, Germany) decreasing the atrial gradient from 8 to 3 mmHg.The baby was weaned from mechanical ventilation in the intensive care unit (ICU) and put under unfractionated heparin (100 UI/kg) and acetylsalicylic acid (5 mg/kg) [3,4].Then, he was sent to the ward in good clinical conditions and with a mild increase in oxygen saturation (from 80 to 85%).Echocardiography performed the day after the procedure revealed a significant improvement of the transatrial flow.However, despite the lack of clinical findings and a normal electrocardiogram (ECG) (Supplementary Figure S1), the pre-discharge echocardiography, performed three days after the procedure, imaged a large thrombus within the native aortic root (Figures 1 and 2, Videos S1 and S2).Thus, the baby was monitored in ICU and put under low weight heparin (LWE) infusion (25 UI/Kg/h) in view of chronic anticoagulation therapy (warfarin 0.2 mg/Kg) [3,4].Partial resolution of the clot was documented after 72 h, and it was completed after 6 days of therapy (Figure 3, Videos S3 and S4).LWE was stopped after 96 h, and the baby was discharged under warfarin therapy after a few days without clinical and instrumental findings.Of interest, no high-sensitivity (hs) troponin-T rise was noted in serial blood test examinations.

Methods
In February 2023, we performed a systematic search in the National Library of Medicine for Medical Subject Headings and free text terms including "native aortic thrombus" and "hypoplastic left heart syndrome".The search was refined by adding keywords for "Fontan palliation" and "univentricular heart".The cases were excluded if the diagnosis of aortic thrombosis was uncertain or performed post mortem.

Methods
In February 2023, we performed a systematic search in the National Library of Medicine for Medical Subject Headings and free text terms including "native aortic thrombus" and "hypoplastic left heart syndrome".The search was refined by adding keywords for "Fontan palliation" and "univentricular heart".The cases were excluded if the diagnosis of aortic thrombosis was uncertain or performed post mortem.

Methods
In February 2023, we performed a systematic search in the National Library of Medicine for Medical Subject Headings and free text terms including "native aortic thrombus" and "hypoplastic left heart syndrome".The search was refined by adding keywords for "Fontan palliation" and "univentricular heart".The cases were excluded if the diagnosis of aortic thrombosis was uncertain or performed post mortem.

Discussion
Native aortic root thrombosis is a rare potential complication in univentricular heart circulation [1][2][3][5][6][7][8][9][10][11][12][13][14][15] that is particularly worrisome since it has the potential for coronary occlusion, resulting in myocardial ischemia and sudden cardiac death, or for systemic embolism [1][2][3][5][6][7][8][9][10][11][12][13][14][15].Thrombosis in the native aorta has been described only in HLHS with stenotic inflow and/or outflow pathways [1][2][3][5][6][7][8][9][10][11][12][13][14][15].It may be due to low-flow dynamics inside the left cardiac chambers due to the preferential flow to the right heart chambers in the setting of unrestrictive atrial septal fenestration.In our patient, restrictiveness of the PFO could have forced the blood flow across the left heart pathway, hindering clot formation.At the time of atrial stenting and left heart decompression, the sudden decrease in the blood flow amount and velocity along the left ventricle might have contributed to the thrombosis.The presence of an anterograde flow through a stenotic aortic valve does not seem protective itself [10], rather if the anterograde flow is scarce and at low pressure may compete with the regrade flow creating an area of stasis favoring thrombus formation [10].We suppose that in our case, before atrial stenting procedure due the stenotic PFO, part of the pulmonary vein flow was forced across the mitral valve and subsequently to the aortic valve (which was of a discrete size for the pathology); thus, the anterograde flow had a pressure enough not to create stasis with the retrograde flow.After the procedure, the flow across the pulmonary veins had a preferential pathway across the PFO; thus, mitral and aortic flow became minimal, favoring clot formation.In this patient, the thrombus was very close to the coronary arteries, and in some images, it may seem to partly obstruct the left coronary artery origin.The risk of myocardial ischemia due either to occlusion or embolization into the vessels was a major concern, although neither an electrocardiograph sign of myocardial ischemia, nor an hs-troponin-T increase was found during continuous monitoring.
In our case, the formation of thrombus in the native aorta not only happened with a child completely asymptomatic but also quite unexpectedly after a procedure that theoretically should have improved the hemodynamic balance.The formation of the clot was not related to hypercoagulability due to cardiac catheterization procedure, as one may initially hypothesize, since it was not present the day after the procedure.Rather it was due to a rapid change in the hemodynamics, with a diminished anterograde aortic flow.
Diagnosis is generally feasible with transthoracic echocardiography [1,2,6,7,[9][10][11][12], but experience and a careful and systematic assessment of the native aorta are required.The increased awareness of this rare complication has led to an increasing diagnostic rate in the past few years [4,[10][11][12], with multiple cases described.In the case we described, the prompt diagnosis at a routine pre-discharge transthoracic echocardiogram and the subsequent therapeutic management made it possible to avoid potentially life-threatening coronary complications.This indicates the importance of systematic echocardiographic investigation of the native aorta as a potential site for thrombus formation in patients with HLHS and hypoplastic inflow and outflow pathways, even when hemodynamic and clinical conditions seem to be optimal [1][2][3][5][6][7][8][9][10][11][12][13][14][15].

Table 1 .
Studies reporting thrombus in native aorta of HLHS.